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 MW CH402 questions and answers from 2010 paper:

1. Answer ALL parts.

(a) Describe two approaches to molecule 1, in each case showing which bond adjacent
to the chiral centre would be created. Specific mechanisms and reagents are not
required.
O
Ph
H

1
Looking for; (i) protonation of an enolate, (ii) alkylation of an enolate
with BnBr, (iii) ring opening cyclohexene oxide with BnMgBr then oxidation
or (iv) any other suitable method. One mark each.
[10%]

(b) The heterocyclic compound 2 can be used to catalyse the addition of PhCH2Br to 3
to give the enantiomerically enriched product 4.

10 mol%
Ph Ph
O O Ph
N H
H
2

PhCH2Br 96% ee
3 4

Given this information;

(i) Illustrate the intermediate that will be formed upon reaction of 2 with 3, and
give a mechanism for its formation.
[15%]
 intermediate, formed via:
Ph Ph Ph Ph Ph Ph Ph Ph
N N N N
H O
H OH H OH2

intermediate, formed via: intermediate, formed via:

Ph Ph Ph Ph Ph Ph
N N N
OH2
H

2 marks for mechanism and 1 for product.

(ii) Explain, with the aid of appropriate illustrations, how the catalyst
subsequently controls the absolute configuration of the product.
[15%]
The upper face is blocked and
Ph Ph Ph Ph alkylation goes on lower face
N N O
H Ph H Ph
Br

Ph hydrolysis

1 mark for illustration, 1 for explanation, 1 for mention of hydrolysis.

(iii) Explain why the use of 2 to catalyse the addition of phenylcuprate to 5

gives the product 6 with a much lower ee.

10 mol%
O Ph Ph O
N
H 50% ee
2
Ph
Ph2CuLi
5 6 H

[10%]

In this case a similar intermediate forms as in (ii) however the CH2Ph group is further from
the centre to which the Ph- adds hence it exerts less control. 2 marks.

This is the full question:

2. Answer ALL parts.
(a) The Sharpless Asymmetric Dihydroxylation (AD) reaction converts styrene 7 into
diol 8 in high ee.
HO
OH
10 mol% Chiral amine
5 mol% OsO4

NaIO4
7 8
Given this information;

(i) Devise a synthesis of allylic alcohol 10 from alkene 9. Reagents should be

given for each step, but mechanisms need not be illustrated.

OH

F3C F3C
9 10
OH
O OH
OH
OH

AD oxidation Wittig

(e.g. PCC, or similar

F3C F3C F3C
Swern)
9 F3C 10
One park per step, don’t want to get bogged down with selectivity of oxidation or protecting
groups. Looking for concept.
[15%]

(ii) Devise a synthesis of ester 12 from alkene 11. Reagents should be given for
each step, but mechanisms need not be illustrated.
O

Ph O
Me
H
O O

O O
11 12
 O O
HO Ph O Ph O
OH OH Me
H
O PhCOCl i) OH to OTs
AD O O with TsCl. O

O O ii) Me2CuLi
O O
11 12
One mark per step above.
[15%]

(b) Cationic complex 13 ([(chiraphos)Rh]+) acts as an asymmetric catalyst for the

hydrogenation of α-acylaminoacrylate 14 to give the amino acid precursor 15 in
high ee.
Ph Ph
O 0.1 mol% O H
PPh2 catalyst 13
Ph2P
Me N CO2H Me N CO2H
Rh H H
MeOH, H2
13 14 15

(i) Illustrate how the phenyl rings in 13 create a chiral environment around the
rhodium(I) atom.

The arene rings are

P P edge and face oriented.
Rh

2 marks.
[10%]

(ii) Illustrate the two diastereoisomers which are formed upon co-ordination of
substrate 14 to complex 13.

Ph
O Ph
P Rh P O
P Rh P
Me N CO2H
H HO2C N Me
H

2 marks for each diastereoisomeric complex.

[20%]

(iii) Explain how the catalyst thus achieves a selective hydrogenation of 14.
The diastereoisomers are of different energies (1 mark) and therefore of
different relative abundances (1 mark) and different reactivities (1 mark).
The hydrogen gas first goes onto the Rh and is transferred preferentially to
 the proximal face of the alkene in the more reactive (but less abundant)
complex (1 mark) which is presumably the left hand one above.
[20%]

(iv) Devise a synthetic sequence for the synthesis of the α-arylpropionic acid 15
from methyl ester 16, using complex 13 in a hydrogenation step. Reagents
should be given, but mechanisms need not be illustrated.
Me H
MeO HO

O O
16 15

MeO MeO HO
CH2O, Me2NH hydrolysis
O O O
16
The acid group in the hydrogenation Asymmetric hydrogenation
substrate co-ordinates to Rh(I) in an using 13.
analogous mode to 14, thus directing Me H
the reaction. HO
One mark per step and one for explanation.
O
15

[20%]
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CH402

2006-2007

Course taught by P. C. Taylor.

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